Role of heparan sulfatases in ovarian and breast cancer

Endosulfatases HSulf-1 and -2 (also referred to as Sulf1 and -2) represent a family of enzymes that modulate heparin binding growth factor signaling. Heparan sulfatase 1 (HSulf-1) and heparan sulfatase 2 (HSulf-2) are two important 6-O endosulfatases which remove or edit 6-O sulfate residues of N-glucosamine present on highly sulfated HS. Alteration of heparan sulfatases have been identified in the context of several cancer types. Many cancer types either exhibit increased or decreased HSulfs expression at the transcript levels. Specifically, HSulf-1 was found to be downregulated in early-stage ovarian tumors, hepatocellular carcinoma, and metastatic breast cancer patients. HSulf-2 was found to be upregulated in ductal carcinoma in situ and invasive ductal carcinoma, whereas limited information is present about HSulf-2 expression in different stages of ovarian cancers. Here, we review the important role of these sulfatases play in ovarian and breast cancers in terms of tumorigenesis such as angiogenesis, chemoresistance, apoptosis, growth factor signaling, hypoxia and metastasis. These recent discoveries have added significant understanding about these sulfate editing enzymes.